Developing New Drugs

to Control TB
William Wells, Ph.D.
Director, Market Access
Global Alliance for TB Drug Development (TB Alliance)

Journalist to Journalist Project, IUATLD Meeting

Cancun, Mexico, December 4, 2009
 The need for new TB drugs

• The need to ensure adherence can put a huge burden on patients

• Shorter therapies equals > adherence, > cure, < burden on patients, and <
emergence of drug resistance
 Current TB Therapy and Unmet Needs
Current Therapy Unmet Needs
 Drug-sensitive TB  Shorter therapy
4 Drugs, ≥6 months

 M(X)DR-TB  More effective, safer drugs;

Few drugs (including injectables); shorter, simpler therapy
≥18 months; severe side effects

 TB/HIV co-infection  Co-administration with ARVs

Drug-drug interactions with ARVs
(antiretroviral agents – i.e.,
HIV/AIDS drugs)

 Latent TB Infection  Shorter therapy

9 months of isoniazid

No new drugs for TB in 40 years; no market incentive

 TB Alliance
• Founded in 2000 GOVERNMENTS

• Not-for-profit Product PHARMA

BIOTECH

Development Partnership
(PDP) headquartered in New
York, with offices in Brussels TB
and Pretoria Alliance

• Entrepreneurial, virtual drug ACADEMIA INSTITUTES

development approach
• Largest portfolio of TB drug FOUNDATIONS

candidates in history
 Operating Model
A flexible, virtual R&D approach:

 In-licensing and independent development

PA-824 (Chiron/Novartis)

 Collaborative R&D with affordability commitment

Moxifloxacin (Bayer); GSK mini portfolio (GSK); TB drug portfolio (Novartis);
TMC-207 (J&J)

 Contracted R&D with IP rights

Quinolone (KRICT); Nitroimidazole (ACSRC); Riminophenazine (IMM);
Phenotypic screening (UIC); Energy metabolism (UPenn); Protease (IDRI);
Tryptanthrine (KRICT); RNAP (Rutgers); LeuRS (Anacor); Menaquinone (CSU);
Topo I (NYMC); Natural products (IMCAS)
 Why are PDPs needed?
 There is a “market failure” for diseases found solely or predominantly in low
income countries

 Private sector:
 Cannot justify such large expenditure when the returns are so low
 Prior to the PDPs, most products that were useful only in low income countries were discovered
by “accident” (e.g., veterinary product) or for military or tourists

 Academic researchers:
 Publicly funded
 Have the interest in pursuing neglected diseases
 But do not have the means to do so (large chemical libraries, screening facilities, networks of
trials sites and the staff to run them)
Private investment is not enough to support TB R&D

TB R&D funding by
sector, 2008

 Funding for all TB R&D (basic, drugs, diagnostics, vaccines, operational)

is US$510m per year, compared to the US$2 billion per year estimated to
be needed to reach Global Plan to Stop TB targets
 TB Alliance Vision
FD
Cs

10 days
2 – 4 months

Success will require novel

6 – 30 months
multi-drug combinations
Global Clinical Portfolio - New TB
Drugs in Registration Programs
Oflotub, TDR
Oflotub, TDR

Bayer, TB Alliance
Bayer, TB Alliance

Tibotec, TB Alliance
Tibotec, TB Alliance

Otsuka
Otsuka

TB Alliance
TB Alliance

Sequella
Sequella

Lupin
Lupin

Pfizer
Pfizer

Phase I Phase II Phase III

Phase I Phase II Phase III
 TB Alliance Market Access
 Focused on the AAA strategy:
 Available (supply chain, forecasting, registration, distribution strategy);
 Affordable (pricing strategy, donor policies);
 Adopted (issues and evidence for key decision makers).

 Ensure that products are suited for, and wanted by, those in endemic markets.

 Formulate strategy, but work through partners and existing structures.

 Need to understand the process so we can facilitate coordination.
 WHO recommendation is essential.
 Existing Ministry of Health and NGO programs will deliver the drugs.
 Demand Forecast
Define issues
Understand the regimen
(Moxi Demand Forecast) for users
(Value Proposition Study)
change process
Understand (Country Introduction Study)
Existing Market
(Market Study) Devise local launch
strategy
Manufacturing
Strategy Market • Stakeholder and partner
mapping and engagement

IP agreements Access • Document resources

for operational research,

Pricing Strategy
Strategy financing, TA, retraining

Consumer marketing
Regulatory Strategy
Support local
Engage funding
Engage guideline- decision-making
and procurement
setting agencies (cost-benefit)
agencies
(WHO and others)
Market Study
Conducted with IMS Health
Published May 2007

 Map TB drug market in 6 key high

burden & 4 high income countries
 Understand flow of drugs to
prepare for launch
 Fragmented, local markets

 Size the existing global TB drug

market
 Estimate to inform TB Alliance deals
and strategy
 Global market of ~US$315m including
all four first-line drugs
What Countries Want
Value Proposition Study
Published August 2009

Most stakeholders would welcome treatment

shortening as the primary goal.
Unacceptable trade-offs in all countries:
• Decreased efficacy
• Additional safety concerns or side effects requiring
monitoring or expensive adjuvant therapies
• Significant drug interactions with other commonly-
used drugs (including ARVs)
Unacceptable trade-offs in some countries:
• Treatment frequency significantly different from
current TB program (e.g., India)
• Unavailability in fixed-dose combination (FDC)
 Summary
 Great need for new drugs to address the
challenges and unmet needs in TB therapy
 Resurgence in TB drug R&D; up to 2-3 new
drugs could reach registration by 2015
 Increased funding is needed to support a
stronger global TB drug pipeline and fulfill our
vision
Thank You
 REMoxTB Trial Design
Randomized, double-blind; non-inferiority
Treatment Duration (months)
1 2 3 4 5 6
Intensive Continuation

800 participants
HRZE HR
Standard regimen
Placebos
800 participants
Moxifloxacin HRZM HRM
for
Ethambutol Placebos
800 participants
Moxifloxacin MRZE MR
for
Isoniazid Placebos

All pts followed for 12 months post-treatment end